Adult polyglucosan body disease
Updates to Article Attributes
Adult polyglucosan body disease (APBD) is a very rare adult-onset form of glycogen storage disease type IV with characteristic clinicoradiological features.
Epidemiology
Adult polyglucosan body disease is considered very rare 1,2, but the exact incidence is not known and it may be often misdiagnosed and thus underdiagnosed 1. It is particularly common in Ashkenazi Jews, however, has been described in other ethnicities and is likely panethnic 1-4. There is no known sex predilection 1. The median age of onset is approximately 50 years 1.
Clinical presentation
The most common clinical features in adult polyglucosan body disease reflect a neurological syndrome incorporating a dorsolateral myelopathy and a predominantly axonal sensorimotor peripheral polyneuropathy 1-4:
-
neurogenic bladder dysfunction
usually the first symptom to manifest
-
spastic paraplegia with gait dysfunction
often associated with spinal proprioceptive and vibration loss, and upper motor neurone signs
weakness may also be contributed to by neuropathy
upper limbs are involved later than lower limbs
length-dependent sensory loss and paraesthesias
Less common clinical features include 1-4:
faecal incontinence
attentional and memory deficits, often mild
-
autonomic dysfunction
orthostatic hypotension
erectile dysfunction in males
neuro-ophthalmological anomalies such as saccadic pursuit or impaired convergence
cerebellar ataxia
bradykinesia and parkinsonism
Unlike other phenotypes of glycogen storage disease IV, hepatic involvement is very rare in adult polyglucosan body disease 2.
Pathology
Genetics
Adult polyglucosan body disease is an autosomal recessive condition caused by mutation in the GBE1 gene on chromosome 3p12.2, with the most implicated mutation being the missense mutation p.Y329S which is particularly common within the Ashkenazi Jewish population 1-4. GBE1 normally encodes for the glycogen branching enzyme (GBE) and mutation to GBE1 results in a reduction in GBE activity, usually to <25% of normal 1,2. This causes an accumulation of polyglucosan inclusions in various bodily tissues, including, and most importantly, within the central and peripheral nervous systems, leading to the clinical phenotype 1,2.
Markers
GBE activity can be measured in peripheral leucocytes or skin fibroblasts 1.
Radiographic features
MRI
Brain
MRI brain is always abnormal 1,4. In nearly all patients, there is evidence of leukoencephalopathy with confluent and/or multifocal, symmetrical periventricular white matter abnormalities with an occipital predominance 1,3. Additionally, nearly all patients have signal abnormalities affecting the medial lemniscus and corticospinal tracts through the brainstem, and most patients have signal abnormalities of the posterior limb of the internal capsule (often sparing the anterior limb) and the external capsule1,3. The medulla oblongata is nearly always atrophied, and there may be atrophy of the cerebellar vermis, corpus callosum, and less commonly of other supratentorial structures 1.
In structures with signal abnormalities, the signal characteristics are 1:
T1: iso-intense or hypointense
T2/FLAIR: hyperintense
Spinal cord
The most common anomaly is spinal cord atrophy, affecting the entire length of the spinal cord1,3-5. Within the spinal cord, signal change has rarely been reported, but there may be increased T2 signal within the dorsal columns5.
Treatment and prognosis
There is no disease modifying therapy available 2,6, and thus, management is symptomatic (e.g. indwelling catheter for urinary retention, gait aids for mobility, etc.) 2. However, due to frequent misdiagnosis, many patients are initiated on treatments of other conditions (e.g. pharmacotherapy for benign prostatic hyperplasia or immunosuppressive therapy for multiple sclerosis) 4.
Prognosis and quality of life is variable depending on the severity of the clinical syndrome and supports available, but the median survival is reduced at approximately 70 years 1,2.
History and etymology
Adult polyglucosan body disease was first described in a 1980 seminal case series 7.
Differential diagnosis
causes of cerebral small vessel disease (e.g. CADASIL)
other causes of leukoencephalopathy or adult leukodystrophy
- +<p><strong>Adult polyglucosan body disease (APBD)</strong> is a very rare adult-onset form of <a href="/articles/glycogen-storage-disease-type-iv" title="glycogen storage disease type IV">glycogen storage disease type IV</a> with characteristic clinicoradiological features.</p><h4>Epidemiology</h4><p>Adult polyglucosan body disease is considered very rare <sup>1,2</sup>, but the exact incidence is not known and it may be often misdiagnosed and thus underdiagnosed <sup>1</sup>. It is particularly common in Ashkenazi Jews, however, has been described in other ethnicities and is likely panethnic <sup>1-4</sup>. There is no known sex predilection <sup>1</sup>. The median age of onset is approximately 50 years <sup>1</sup>.</p><h4>Clinical presentation </h4><p>The most common clinical features in adult polyglucosan body disease reflect a neurological syndrome incorporating a dorsolateral myelopathy and a predominantly axonal sensorimotor peripheral polyneuropathy <sup>1-4</sup>:</p><ul>
- +<li>
- +<p><a href="/articles/neurogenic-bladder" title="Neurogenic bladder">neurogenic bladder</a> dysfunction</p>
- +<ul><li><p>usually the first symptom to manifest</p></li></ul>
- +</li>
- +<li>
- +<p>spastic paraplegia with gait dysfunction</p>
- +<ul>
- +<li><p>often associated with spinal proprioceptive and vibration loss, and upper motor neurone signs</p></li>
- +<li><p>weakness may also be contributed to by neuropathy</p></li>
- +<li><p>upper limbs are involved later than lower limbs</p></li>
- +</ul>
- +</li>
- +<li><p>length-dependent sensory loss and paraesthesias</p></li>
- +</ul><p>Less common clinical features include <sup>1-4</sup>:</p><ul>
- +<li><p>faecal incontinence</p></li>
- +<li><p>attentional and memory deficits, often mild</p></li>
- +<li>
- +<p>autonomic dysfunction</p>
- +<ul>
- +<li><p>orthostatic hypotension</p></li>
- +<li><p><a href="/articles/erectile-dysfunction" title="Erectile dysfunction">erectile dysfunction</a> in males</p></li>
- +</ul>
- +</li>
- +<li><p>neuro-ophthalmological anomalies such as saccadic pursuit or impaired convergence</p></li>
- +<li><p>cerebellar <a href="/articles/ataxia-clinical-sign" title="Ataxia (clinical sign)">ataxia</a></p></li>
- +<li><p>bradykinesia and parkinsonism</p></li>
- +<li><p><a href="/articles/cardiomyopathy-1" title="Cardiomyopathy">cardiomyopathy</a></p></li>
- +</ul><p>Unlike other phenotypes of glycogen storage disease IV, hepatic involvement is very rare in adult polyglucosan body disease <sup>2</sup>.</p><h4>Pathology</h4><h5>Genetics</h5><p>Adult polyglucosan body disease is an autosomal recessive condition caused by mutation in the <em>GBE1</em> gene on chromosome 3p12.2, with the most implicated mutation being the missense mutation p.Y329S which is particularly common within the Ashkenazi Jewish population <sup>1-4</sup>. <em>GBE1</em> normally encodes for the glycogen branching enzyme (GBE) and mutation to <em>GBE1</em> results in a reduction in GBE activity, usually to <25% of normal <sup>1,2</sup>. This causes an accumulation of polyglucosan inclusions in various bodily tissues, including, and most importantly, within the central and peripheral nervous systems, leading to the clinical phenotype <sup>1,2</sup>.</p><h5>Markers</h5><p>GBE activity can be measured in peripheral leucocytes or skin fibroblasts <sup>1</sup>.</p><h4>Radiographic features</h4><h5>MRI</h5><h6>Brain</h6><p>MRI brain is always abnormal <sup>1,4</sup>. In nearly all patients, there is evidence of leukoencephalopathy with confluent and/or multifocal, symmetrical periventricular white matter abnormalities with an occipital predominance <sup>1,3</sup>. Additionally, nearly all patients have signal abnormalities affecting the <a href="/articles/medial-lemniscus" title="Medial lemniscus">medial lemniscus</a> and <a href="/articles/corticospinal-tract" title="Corticospinal tract">corticospinal tracts</a> through the <a href="/articles/brainstem" title="Brainstem">brainstem</a>, and most patients have signal abnormalities of the posterior limb of the <a href="/articles/internal-capsule" title="Internal capsule">internal capsule</a> (often sparing the anterior limb) and the <a href="/articles/external-capsule" title="External capsule">external capsule</a> <sup>1,3</sup>. The <a href="/articles/medulla-oblongata" title="Medulla oblongata">medulla oblongata</a> is nearly always atrophied, and there may be atrophy of the <a href="/articles/vermis" title="Cerebellar vermis">cerebellar vermis</a>, <a href="/articles/corpus-callosum" title="Corpus callosum">corpus callosum</a>, and less commonly of other supratentorial structures <sup>1</sup>.</p><p>In structures with signal abnormalities, the signal characteristics are <sup>1</sup>:</p><ul>
- +<li><p><strong>T1:</strong> iso-intense or hypointense</p></li>
- +<li><p><strong>T2/FLAIR:</strong> hyperintense</p></li>
- +</ul><h6>Spinal cord</h6><p>The most common anomaly is spinal cord atrophy, affecting the entire length of the <a href="/articles/spinal-cord" title="Spinal cord">spinal cord</a> <sup>1,3-5</sup>. Within the spinal cord, signal change has rarely been reported, but there may be increased T2 signal within the <a href="/articles/dorsal-columns" title="Dorsal columns">dorsal columns</a> <sup>5</sup>.</p><h4>Treatment and prognosis</h4><p>There is no disease modifying therapy available <sup>2,6</sup>, and thus, management is symptomatic (e.g. indwelling catheter for urinary retention, gait aids for mobility, etc.) <sup>2</sup>. However, due to frequent misdiagnosis, many patients are initiated on treatments of other conditions (e.g. pharmacotherapy for <a href="/articles/benign-prostatic-hyperplasia" title="Benign prostatic hyperplasia">benign prostatic hyperplasia</a> or immunosuppressive therapy for <a href="/articles/multiple-sclerosis" title="Multiple sclerosis">multiple sclerosis</a>) <sup>4</sup>.</p><p>Prognosis and quality of life is variable depending on the severity of the clinical syndrome and supports available, but the median survival is reduced at approximately 70 years <sup>1,2</sup>.</p><h4>History and etymology</h4><p>Adult polyglucosan body disease was first described in a 1980 seminal case series <sup>7</sup>.</p><h4>Differential diagnosis</h4><ul>
- +<li><p><a href="/articles/hereditary-spastic-paraplegia" title="Hereditary spastic paraplegia">hereditary spastic paraplegia</a></p></li>
- +<li><p><a href="/articles/adrenomyeloneuropathy" title="Adrenomyeloneuropathy">adrenomyeloneuropathy</a></p></li>
- +<li><p><a href="/articles/alexander-disease" title="Alexander disease">adult-onset Alexander disease</a></p></li>
- +<li><p>causes of <a href="/articles/cerebral-small-vessel-disease" title="Cerebral small vessel disease">cerebral small vessel disease</a> (e.g. <a href="/articles/cerebral-autosomal-dominant-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy-cadasil-1" title="Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)">CADASIL</a>)</p></li>
- +<li><p><a href="/articles/multiple-sclerosis" title="Multiple sclerosis">multiple sclerosis</a></p></li>
- +<li><p><a href="/articles/amyotrophic-lateral-sclerosis-3" title="Amyotrophic lateral sclerosis">amyotrophic lateral sclerosis</a></p></li>
- +<li><p>other causes of leukoencephalopathy or <a href="/articles/adult-leukodystrophies" title="Adult leukodystrophies">adult leukodystrophy</a></p></li>
- +</ul>
References changed:
- 1. Mochel F, Schiffmann R, Steenweg M et al. Adult Polyglucosan Body Disease: Natural History and Key Magnetic Resonance Imaging Findings. Ann Neurol. 2012;72(3):433-41. <a href="https://doi.org/10.1002/ana.23598">doi:10.1002/ana.23598</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/23034915">Pubmed</a>
- 2. Koch R, Soler-Alfonso C, Kiely B et al. Diagnosis and Management of Glycogen Storage Disease Type IV, Including Adult Polyglucosan Body Disease: A Clinical Practice Resource. Mol Genet Metab. 2023;138(3):107525. <a href="https://doi.org/10.1016/j.ymgme.2023.107525">doi:10.1016/j.ymgme.2023.107525</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/36796138">Pubmed</a>
- 3. Gayed M, Sgobbi P, Pinto W, Kishnani P, Koch R. Case Report: Expanding the Understanding of the Adult Polyglucosan Body Disease Continuum: Novel Presentations, Diagnostic Pitfalls, and Clinical Pearls. Front Genet. 2023;14:1282790. <a href="https://doi.org/10.3389/fgene.2023.1282790">doi:10.3389/fgene.2023.1282790</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/38164512">Pubmed</a>
- 4. Hellmann M, Kakhlon O, Landau E et al. Frequent Misdiagnosis of Adult Polyglucosan Body Disease. J Neurol. 2015;262(10):2346-51. <a href="https://doi.org/10.1007/s00415-015-7859-4">doi:10.1007/s00415-015-7859-4</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/26194201">Pubmed</a>
- 5. López Chiriboga A. Teaching Neuro <i>Images</I> : Prominent Spinal Cord Atrophy and White Matter Changes in Adult Polyglucosan Body Disease. Neurology. 2017;88(20):e194-5. <a href="https://doi.org/10.1212/wnl.0000000000003945">doi:10.1212/wnl.0000000000003945</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/28507268">Pubmed</a>
- 6. Stavros K. Genetic Myelopathies. CONTINUUM: Lifelong Learning in Neurology. 2024;30(1):119-32. <a href="https://doi.org/10.1212/con.0000000000001377">doi:10.1212/con.0000000000001377</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/38330475">Pubmed</a>
- 6. Stavros K. Genetic Myelopathies. CONTINUUM: Lifelong Learning in Neurology. 2024;30(1):119-32. <a href="https://doi.org/10.1212/con.0000000000001377">doi:10.1212/con.0000000000001377</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/38330475">Pubmed</a>
- 7. Robitaille Y, Carpenter S, Karpati G, DiMauro S. A Distinct Form of Adult Polyglucosan Body Disease with Massive Involvement of Central and Peripheral Neuronal Processes and Astrocytes: A Report of Four Cases and a Review of the Occurrence of Polyglucosan Bodies in Other Conditions Such as Lafora's Disease and Normal Ageing. Brain. 1980;103(2):315-36. <a href="https://doi.org/10.1093/brain/103.2.315">doi:10.1093/brain/103.2.315</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/6249438">Pubmed</a>
- 6. Robitaille Y, Carpenter S, Karpati G, DiMauro S. A Distinct Form of Adult Polyglucosan Body Disease with Massive Involvement of Central and Peripheral Neuronal Processes and Astrocytes: A Report of Four Cases and a Review of the Occurrence of Polyglucosan Bodies in Other Conditions Such as Lafora's Disease and Normal Ageing. Brain. 1980;103(2):315-36. <a href="https://doi.org/10.1093/brain/103.2.315">doi:10.1093/brain/103.2.315</a> - <a href="https://www.ncbi.nlm.nih.gov/pubmed/6249438">Pubmed</a>
Tags changed:
- cases
Systems changed:
- Central Nervous System